Quantitative structure-activity relationship analysis of acute toxicity of diverse chemicals to Daphnia magna with whole molecule descriptors

Quantitative structure-activity relationship analysis and estimation of toxicological effects at lower-mid trophic levels provide first aid means to understand the toxicity of chemicals. Daphnia magna serves as a good starting point for such toxicity studies and is also recognized for regulatory use in estimating the risk of chemicals. The ECOTOX database was queried and analysed for available data and a homogenous subset of 253 compounds for the endpoint LC50 48 h was established. A four-parameter quantitative structure-activity relationship was derived (coefficient of determination, r(2) = 0.740) for half of the compounds and internally validated (leave-one-out cross-validated coefficient of determination, r(cv)(2) = 0.714; leave-many-out coefficient of determination, r(LMO)(2) = 0.738). External validation was carried out with the remaining half of the compounds (coefficient of determination for external validation, r(ext)(2) = 0.634). Two of the descriptors in the model (log P, average bonding information content) capture the structural characteristics describing penetration through bio-membranes. Another two descriptors (energy of highest occupied molecular orbital, weighted partial negative surface area) capture the electronic structural characteristics describing the interaction between the chemical and its hypothetic target in the cell. The applicability domain was subsequently analysed and discussed.